Chronic therapies involving protein or peptide drugs to treat conditions such as diabetes, cancer, hepatitis, and osteoporosis represent the continuing shift of the pharmaceutical industry toward biotherapeutics. Due to lifestyle issues and an aging population, the number of patients requiring these medications is growing rapidly. Health care economics often require these agents to be administered without office visits, mandating the need for formulations that allow for subcutaneous (SC) injection, rather than intravenous (IV) infusion. No predictive model for SC injection outcomes in man has been identified; the prospect of clinically testing a number of formulations is prohibitively expensive. Thus, development programs for many promising agents are often halted when formulations identified with sufficient shelf-life stability and sufficient preclinical efficacy result in low or variable bioavailability (% BA) following SC injection when tested in the clinic. Such outcomes result in significant lost opportunity costs, imparting a substantial addition to research and development costs that are ultimately reflected in drug pricing, which impacts overall healthcare expenses.
There are several reasons for this state of the affairs. The first is that there is limited knowledge of what a protein or peptide in a formulation experiences during the critical first hour following administration, in particular by subcutaneous injection, and without this information, formulation scientists cannot design formulations to take account of these processes. Thus, rather than addressing the problem of understanding what happens when a biotherapeutic is administered, formulation scientists and regulatory authorities can only focus on extending the shelf life of the formulation prior to administration by attempting to minimise conflicting chemical and physical degradation pathways and to hope that this is compatible for (e.g.) subcutaneous injection. Current subcutaneously administered formulations typically have a 2 to 3 year shelf life using pH 5-6 and various combinations excipients such as detergents, preservatives, sugars and/or human albumin. However, with no information regarding the events that take place on administration and at the injection site, there is no systematic approach to address problem of poor or variable bioavailability through formulation changes. The present invention attempts to address this unmet need in the art.
U.S. Pat. No. 4,812,407 describes an apparatus for testing the diffusion behaviour of a drug in which a radiolabelled drug is introduced into a donor compartment and allowed to diffuse through a membrane into a surrounding acceptor compartment. A measuring device such as a scintillation counter is used to detect the quantity or concentration of the radiolabelled drug in the acceptor compartment.
EP 2182342 discloses an apparatus and method for testing dissolution of a drug using a chamber with two compartments separated by a membrane which is permeable to dissolved drug, but impermeable to the drug in an undissolved form. A similar approach is disclosed in WO 00/46597.